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Digestive System
Structure, Absorption & Regulation

Master GI tract anatomy, nutrient absorption mechanisms, and hormonal regulation for MCAT Biological Foundations.

MCAT Bio/Biochem

The Alimentary Canal: A Continuous Tube

The gastrointestinal (GI) tract is a continuous muscular tube extending from the mouth to the anus. Each region has specialized structure and function. The four tissue layers: mucosa, submucosa, muscularis externa, and serosa: are present throughout but vary in composition by organ.

The GI Tract Pathway

Mouth Pharynx Esophagus Stomach Small Intestine Large Intestine Salivary Glands Liver / Gallbladder Pancreas Amylase, mucus Bile salts, detox Enzymes, bicarbonate Legend Transport / Mix Chemical Digestion Primary Absorption

Four Tissue Layers of the GI Wall

1. Mucosa
Epithelium + lamina propria + muscularis mucosae. Site of secretion and absorption.
2. Submucosa
Dense connective tissue with Meissner's plexus (submucosal plexus), blood vessels, and glands.
3. Muscularis
Inner circular + outer longitudinal smooth muscle. Contains Auerbach's plexus (myenteric). Drives peristalsis.
4. Serosa
Outermost connective tissue layer (visceral peritoneum). Reduces friction.

Stomach: Gastric Secretions

Parietal Cells
Secrete HCl and intrinsic factor. HCl activates pepsinogen and kills bacteria. \( \text{pH: } 1.5 \text{ to } 3.5 \).
Chief Cells
Secrete pepsinogen, which is cleaved by HCl to form pepsin (protein digestion).
G Cells
Secrete gastrin into the blood, stimulating parietal cells to produce more HCl.

Small Intestine: Three Segments

Duodenum
\( \sim 25 \text{ cm} \)
Receives bile + pancreatic juice Neutralizes acid Iron, calcium Jejunum
\( \sim 2.5 \text{ m} \)
Primary site of nutrient absorption Sugars, amino acids, fatty acids, vitamins Ileum
\( \sim 3.5 \text{ m} \)
Absorbs remaining nutrients Vitamin B12, bile salts Peyer's patches (immune) Surface area amplifiers: Circular folds → Villi → Microvilli (brush border)

Absorption Mechanisms

1
Monosaccharides: Glucose and galactose via \( \text{Na}^+ \)-glucose cotransporter (SGLT1) on apical membrane, then GLUT2 on basolateral. Fructose via GLUT5 (facilitated diffusion).
2
Amino acids: \( \text{Na}^+ \)-dependent cotransport (similar to glucose). Di/tripeptides via PepT1 transporter (\( \text{H}^+ \) cotransport).
3
Fats: Bile salts emulsify fats into micelles. Free fatty acids and monoglycerides diffuse into enterocytes, are re-esterified into triglycerides, packaged into chylomicrons, and enter lacteals (lymph).
4
Water-soluble vitamins: Absorbed in small intestine. Vitamin B12 requires intrinsic factor from parietal cells and is absorbed in the ileum.

Fat Absorption: Micelles to Chylomicrons

GI Lumen Triglycerides Lipase
\( \text{FFA} + \text{Monoglycerides} \)
Bile salts Micelle Enterocyte Diffusion Re-esterify to TG Chylomicron
\( \text{TG} + \text{cholesterol} + \text{ApoB48} \)
Lacteal (Lymph) Exocytosis To thoracic duct → blood NOT portal vein! (Short/medium-chain FA go directly to portal blood)

Mechanical vs. Chemical Digestion

Mechanical Chemical
Definition Physical breakdown into smaller pieces Enzymatic cleavage of covalent bonds
Mouth Mastication (chewing) Salivary amylase (starch), lingual lipase
Stomach Churning / segmentation Pepsin (protein), gastric lipase
Small Intestine Segmentation contractions Pancreatic enzymes, bile salts, brush border enzymes
Bond Changes? No Yes
Surface Area? Increases N/A (reduces polymer size)

Hormonal Regulation of Digestion

Gastrin
Source: G cells (stomach antrum). Trigger: Peptides, distension, vagal input. Effect: Stimulates HCl and pepsinogen secretion, gastric motility.
Secretin
Source: S cells (duodenum). Trigger: Acidic chyme (low pH). Effect: Stimulates pancreatic bicarbonate, inhibits gastric acid.
CCK
Source: I cells (duodenum/jejunum). Trigger: Fats and amino acids. Effect: Stimulates pancreatic enzymes, gallbladder contraction, slows gastric emptying.

More GI Hormones

GIP
Source: K cells (duodenum/jejunum). Trigger: Glucose, fatty acids. Effect: Stimulates insulin release, inhibits gastric acid.
Somatostatin
Source: D cells (stomach, duodenum, pancreas). Effect: Inhibits gastrin, secretin, CCK, insulin, glucagon. The universal "off switch."

Neural Control of Digestion

1
Parasympathetic (vagus nerve): "Rest and digest." Increases motility, secretion, and blood flow to GI tract. Stimulates salivation, gastric acid, and pancreatic secretions.
2
Sympathetic: "Fight or flight." Decreases motility and secretion. Constricts sphincters and redirects blood away from the GI tract.
3
Enteric nervous system (ENS): "The gut brain." Can function independently. Meissner's plexus controls secretion; Auerbach's plexus controls motility.

How to Approach GI Questions

1
Identify the organ: Which part of the GI tract is being discussed? What are its specialized cell types?
2
Identify the nutrient class: Is it carbohydrate, protein, or fat? Each has distinct enzymes and absorption pathways.
3
Determine the signal: What hormone or nerve is regulating the process? What triggered its release?
4
Follow the transport: Where do absorbed molecules go? Portal vein (most nutrients) vs. lacteals/lymph (long-chain fats)?
5
Check feedback loops: Does the product inhibit or stimulate further secretion? Think of negative feedback via somatostatin or low pH inhibiting gastrin.

Worked Example: Starch Digestion

Trace the complete digestion of a starch molecule from mouth to absorption:

1
Mouth: Salivary amylase breaks starch into maltose and dextrins. Optimal \( \text{pH: } \sim 7 \).
2
Stomach: Amylase is inactivated by low pH. No significant carbohydrate digestion occurs here.
3
Duodenum: Pancreatic amylase continues starch breakdown. Brush border enzymes (maltase, isomaltase, sucrase, lactase) produce monosaccharides.
4
Absorption: Glucose enters enterocytes via SGLT1 (apical), exits via GLUT2 (basolateral) into portal blood → liver.

Worked Example: Protein Digestion

1
Stomach: HCl denatures proteins. Pepsin (from pepsinogen) cleaves proteins into large polypeptides. Pepsin works at \( \text{pH } 1.5 \text{ to } 3.5 \).
2
Duodenum: CCK stimulates release of pancreatic proteases: trypsinogen (activated by enterokinase to trypsin), chymotrypsinogen, proelastase, procarboxypeptidase.
3
Activation cascade: Enterokinase activates trypsinogen → trypsin, which then activates all other zymogens.
4
Brush border: Aminopeptidases and dipeptidases yield individual amino acids. Absorbed via \( \text{Na}^+ \)-dependent cotransport into portal blood.

Common Mistakes

✕ Fat goes to portal vein
Long-chain fats are packaged into chylomicrons and enter lacteals (lymph), not the hepatic portal vein. Only short/medium-chain fatty acids go directly to portal blood.
✕ Confusing secretin and CCK
Secretin: triggered by acid, stimulates bicarbonate. CCK: triggered by fats/amino acids, stimulates enzymes and bile. Different triggers, different effects.
✕ Pepsin works everywhere
Pepsin is only active at low pH (\( 1.5 \text{ to } 3.5 \)). In the duodenum, pH is neutralized by bicarbonate, so pepsin is irreversibly inactivated.

Enzyme Summary Table

Enzyme Source Substrate Product
Salivary amylase Salivary glands Starch Maltose, dextrins
Pepsin Chief cells (stomach) Proteins Polypeptides
Trypsin Pancreas Polypeptides Smaller peptides
Lipase Pancreas Triglycerides \( \text{FFA} + \text{monoglycerides} \)
Lactase Brush border Lactose Glucose + galactose
Enterokinase Brush border Trypsinogen Trypsin (active)

Question 1 of 5

A patient has a tumor that destroys the parietal cells of the stomach. Which of the following consequences is most likely?

Question 2 of 5

Which hormone is released in response to acidic chyme entering the duodenum and stimulates the pancreas to secrete bicarbonate?

Question 3 of 5

Long-chain fatty acids are absorbed into enterocytes and ultimately enter the circulation via which route?

Question 4 of 5

A researcher observes that enterokinase activity is blocked in the duodenal brush border. Which process is most directly impaired?

Question 5 of 5

Which nervous system component controls GI motility and is located between the circular and longitudinal muscle layers?